The general hypothesis is that elderly have diminished nutritive flow to skeletal muscle and impaired capacity for building of muscles. In aging populations, this decreased ability to build muscles may represent a tipping point in the progression towards chronic physical frailty and disability. The goal is to examine whether novel pharmacologic therapies can improve nutritive blood flow to the muscles and muscle building in the elderly.

The purpose of this study is 1) to determine if losartan administration will enhance the building of muscles via proteins and suppress muscle breakdown 2) to determine if N-acetylcysteine (NAC) will enhance blood flow to muscles and the building of muscles via proteins.

The investigators will study community dwelling, healthy older men and women (60-85 years). Subjects will be randomized to one of three groups:

Subjects will admit the night before and get their first dose of NAC/ losartan/ placebo with dinner. Subjects will be fasted after 10 pm. The next morning at 6 am blood samples will be taken and leg blood flow (LBF) will be measured. Subjects will receive their second dose of NAC/ losartan/ placebo. As from 6 am every hour blood will be drawn until 1 pm. At 8am, the second biopsy is taken and LFB and CEU will be measured. At 11am they get their third dose of NAC/ losartan/ placebo together with leucine (oral) and again a muscle biopsy is taken and LBF is measured. Leucine is anabolic to skeletal muscle of elderly and so the investigators will use it to stimulate muscle building.

Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:

Lean body mass [ Time Frame: Patients will be in the clinical research center for 24 hours. They admit at 3pm, stay overnight and will be discharged at 3pm the next day. Lean body mass will be measured once, the first day of their 24hr stay at 6pm. ] [ Designated as safety issue: No ]

Lean body mass will be determined by DEXA (GE Lunar iDXA). The same operator will perform all analyses. Whole-body scan will be divided in subregions: Truncal area, android, gynoid, right and left arm, and right and left leg.

Fatigue [ Time Frame: Patients will be in the clinical research center for 24 hours. They admit at 3pm, stay overnight and will be discharged at 3pm the next day. Fatigue will be measured 3 times: the night before, at 9am the next morning and at 1pm. ] [ Designated as safety issue: No ]

Muscle strength will be measured using a Biodex 4 dynamometer, as described above under "Muscle function testing".

Fractional synthetic rate (FSR) [ Time Frame: Patients will be in the clinical research center for 24 hours. They admit at 3pm, stay overnight and will be discharged at 3pm the next day. FSR will be measured 4 times: at 8am, 11 am, noon and 1pm ] [ Designated as safety issue: No ]

Fractional synthetic rate (FSR) of muscle protein synthesis will be measured in the basal and absorptive period during the stable isotope infusion protocol. We will measure changes in basal and absorptive muscle protein synthesis.

Secondary Outcome Measures:

Blood Flow and Muscle Perfusion [ Time Frame: Leg blood flow will be measured 7 times: the night before at 6pm, 6,7,8am and 11,am, noon and 1pm. Perfusion will be measured 3 times: the night before, at 8am and 1pm. ] [ Designated as safety issue: No ]

Signaling pathways involved in muscle protein synthesis and degradation [ Time Frame: Biopsies will be taken 4 times at the second day at 8am, 11 am, noon and 1 pm. ] [ Designated as safety issue: No ]

Muscle morphology and satellite cell activation. [ Time Frame: Patients will be in the clinical research center for 24 hours. They admit at 3pm, stay overnight and will be discharged at 3pm the next day. Biopsies will be taken 4 times at the second day at 8am, 11 am, noon and 1 pm. ] [ Designated as safety issue: No ]

Depression (>5 of the 15 items on the Geriatric Depression Scale (GDS).

Subjects suffering malnutrition or with a BMI < 20 kg/m2 with low albumin or transferrin.

Asthma

Any other condition or event considered exclusionary by the PI and covering faculty physician.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01384591